Identity of the cholesterol-raising factor from boiled coffee and its effects on liver function enzymes.

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      Boiled coffee contains an unidentified lipid that raises serum cholesterol. We studied the effects of the ingestion of coffee oil fractions of increasing purity in volunteers in order to identify the cholesterol-raising factor. In 15 volunteers who ingested 0.75 g/d of a non-triglyceride-fraction from coffee oil for 4 weeks, mean cholesterol increased by 48 mg/dl (1.2 mmol/l) relative to placebo. In contrast, a coffee oil stripped of the non-triglyceride lipids cafestol and kahweol had no effect. In three volunteers, purified cafestol (73 mg/d) plus kahweol (58 mg/d) increased cholesterol by 66 mg/dl (1.7 mmol/l) after 6 weeks. Oil from Robusta beans, which contains cafestol but negligible kahweol, also raised serum cholesterol. These findings show that cafestol is at least partly responsible for the cholesterol-raising effect of boiled coffee. Coffee oils and brews containing cafestol consistently increased serum triglycerides and alanine amino-transferase, and depressed serum creatinine and gamma-glutamyl-transferase (GGT). After withdrawal GGT activity rose above baseline. Norwegians who habitually consumed 5-9 cups of boiled coffee per day had higher serum cholesterol levels and lower GGT but no higher alanine aminotransferase activity than controls. Thus, serum cholesterol is raised by cafestol and possibly also kahweol, both natural components of coffee beans. The mechanism of action is unknown but is accompanied by alterations in liver function enzymes.

      REFERENCES

        • Thelle D.S.
        • Arnesen E.
        • F0rde O.H.
        The Troms0 Heart study.
        Does coffee raise serum cholesterol? N. Engl. J. Med. 1983; 308: 1454-1457
        • Thelle D.S.
        • Heyden S.
        • Fodor J.G.
        Coffee and cholesterol in epidemiological and experimental studies.
        Atherosclerosis. 1987; 67: 97-103
        • B0naa K.
        • Arnesen E.
        • Thelle D.S.
        • F0rde O.H.
        Coffee and cholesterol: is it all in the brewing?.
        The Troms0 study. Br. Med. J. 1988; 297: 1103-1104
        • Stensvold I.
        • Tverdal A.
        • Foss O.P.
        The effect of coffee on blood lipids and blood pressure.
        Results from a Norwegian cross-sectional study, men and women, 40-42 years. J. Clin. Epidemiol. 1989; 42: 877-884
        • Pietinen P.
        • Aro A.
        • Tuomilehto J.
        • Uusitalo U.
        • Korhonen H.
        Consumption of boiled coffee is correlated with serum cholesterol in Finland.
        Int. J. Epidemiol. 1990; 19: 586-590
        • Tverdal A.
        • Stensvold I.
        • Solvoll K.
        • Foss O.P.
        • Lund-Larsen P.
        • Bjartveit K.
        Coffee consumption and death from coronary heart disease in middle-aged Norwegian men and women.
        Sr. Med. J. 1990; 300: 566-569
        • Aro A
        Serum cholesterol levels in Finland and their relationship to changes in coffee brewing methods In Coffee and Coronary Heart Disease with Special Emphasis on the Coffee-Blood Lipids Relationship..
        in: Thelle D.S. van der Stegen G. The Nordic School of Public Health, Goteborg1990: 71-75
        • Salonen J.T.
        • Happonen P.
        • Salonen R.
        • Korhonen H.
        • Nissinen A.
        • Puska P.
        • Tuomilehto J.
        • Vartiainen E.
        Interdependence of associations of physical activity, smoking, and alcohol and coffee consumption with serum high-density lipoprotein and non-high-density lipoprotein cholesterola population study in eastern Finland.
        Prev. Med. 1987; 16: 647-658
        • Arnesen E.
        • F0rde O.H.
        • Thelle D.S.
        Coffee and serum cholesterol.
        Br. Med. J. 1984; 288: 1960
        • F0rde O.H.
        • Knutsen S.F.
        • Arnesen E.
        • Thelle D.S.
        The Troms0 heart study: coffee consumption and serum lipid concentrations in men with hypercholesterol-aemia: a randomized intervention study.
        Br. Med. J. 1985; 290: 893-895
        • Aro A.
        • Tuomilehto J.
        • Kostiainen E.
        • Uusitalo U.
        • Pietinen P.
        Boiled coffee increases serum low density lipoprotein concentration.
        Metabolism. 1987; 36: 1027-1030
        • Bak A.A.A.
        • Grobbee D.E.
        The effect on serum cholesterol levels of coffee brewed by filtering or boiling.
        N. Engl. J. Med. 1989; 321: 1432-1437
        • Aro A.
        • Teirila J.
        • Gref C-G
        Dose-dependent effect on serum cholesterol and apoprotein B concentrations by consumption of boiled, non-filtered coffee.
        Atherosclerosis. 1990; 83: 257-261
        • Fried R.E.
        • Levine D.M.
        • Kwiterovich P.O.
        • Diamond E.L.
        • Wilder L.B.
        • Moy T.F.
        • Pearson T.A.
        The effect of filtered-coffee consumption on plasma lipid levels.
        J. Am. Med. Assoc. 1992; 267: 811-815
        • Rosmarin P.C.
        • Applegate W.B.
        • Somes G.W.
        Coffee consumption and serum lipids: a randomized, crossover clinical trial.
        Am. J. Med. 1990; 88: 349-356
        • Van Dusseldorp M.
        • Katan M.B.
        • Demacker P.N.M.
        Effect of decaffeinated versus regular coffee on serum lipoproteins.
        A 12-week double-blind trial. Am. J. Epidemiol. 1990; 132: 33-40
        • Superko H.R.
        • Bortz Jr., W.
        • Williams P.T.
        • Albers J.J.
        • Wood P.D.
        Caffeinated and decaffeinated coffee effects on plasma lipoprotein cholesterol, apolipoproteins, and lipase activity: a controlled, randomized trial.
        Am. J. Clin. Nutr. 1991; 54: 599-605
        • Van Dusseldorp M.
        • Katan M.B.
        • Van Vliet T.
        • Demacker P.N.M.
        • Stalenhoef A.F.H.
        Cholesterol-raising factor from boiled coffee does not pass a paper filter.
        Arterioscler. Thromb. 1991; 11: 586-593
        • Ahola I.
        • Jauhiainen M.
        • Aro A.
        The hyper-cholesterolaemic factor in boiled coffee is retained by a paper filter.
        J Intern. Med. 1991; 230: 293-297
        • Zock P.L.
        • Katan M.B.
        • Merkus M.P.
        • Van Dusseldorp M.
        • Harryvan J.L.
        Effect of a lipid-rich fraction from boiled coffee on serum cholesterol.
        Lancet. 1990; 335: 1235-1237
      1. Folstar, P. 1976. The composition of wax and oil in green coffee beans. Thesis Agricultural University Wageningen, The Netherlands no. 854.

        • Mensink R.P.
        • Katan M.B.
        Effect of dietary fatty acids on serum lipids and lipoproteins —a metaanalysis of 27 trials.
        Arterioscler. Thromb. 1992; 12: 911-919
        • Viani R.
        Physiologically active substances in coffee In Coffee. Vol 3: Physiology..
        in: Clarke R.J. Macrae R. Elsevier, Applied Science, London and New York1988: 1-31
        • Mensink R.P.
        • Katan M.B.
        Effect of diet enriched with monounsaturated or polyunsaturated fatty acids on levels of low-density and high-density lipoprotein cholesterol in healthy women and men.
        New Engl. J. Med. 1989; 321: 436-441
      2. Cameron M.B. van Staveren W.A. Manual on Methodology for Food Consumption Studies. Oxford University Press, New York1988: 83
        • Keys A.
        • Anderson J.T.
        • Grande F.
        Serum cholesterol response to changes in the diet.
        III. Differences among individuals. Metabolism. 1965; 14: 766-775
        • Folstar P.
        Lipids In Coffee. Vol. 1: Chemistry..
        in: Clarke R.J. Macrae R. Elsevier, Applied Science, London and New York1985: 203-220
      3. Bertholet, R. 1987. Preparation of cafestol. US Patent 4692534

        • Siedel J.
        • Hägele E.O.
        • Ziegenhorn J.
        • Wahlefeld A.W.
        Reagent for the enzymatic determination of serum total cholesterol with improved lipolytic efficiency.
        Clin. Chem. 1983; 29: 1075-1080
        • Warnick G.R.
        • Benderson J.
        • Albers J.J.
        Dextran sulphate-Mg2+ precipitation procedure for quantitation of high-density-lipoprotein cholesterol.
        Clin. Chem. 1982; 28: 1379-1388
        • Sullivan D.R.
        • Kruijswijk Z.
        • West C.E.
        • Kohlmeier M.
        • Katan M.B.
        Determination of serum triglycerides by an accurate enzymatic method not affected by free glycerol.
        Clin. Chem. 1982; 31: 1227-1228
        • Fossati P.
        • Prencipe L.
        Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide.
        Clin. Chem. 1982; 28: 2077-2080
        • Friedewald W.T.
        • Levy R.I.
        • Fredrickson D.S.
        Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of preparative ultracentrifuge.
        Clin. Chem. 1972; 18: 499-502
        • Bartels H.
        • Böhmer M.
        • Heierli C.
        Serum Kreatinin-bestimmung ohne Enteiweissen.
        Clin. Chim. Acta. 1972; 37: 193-197
        • Anonymous
        Empfehlungen der Deutschen Gesellschaft für Klinische Chemie Standard-methode zur Bestimmung der Aktivität der Creatin-Kinase.
        J. Clin. Chem. Clin. Biochem. 1977; 15: 249-254
        • Jendrassik L.
        • Grof P.
        Vereinfachte photometrische Methoden zur Bestimmung des Blutbilirubins.
        Biochem. Z. 1938; 297: 81-89
        • Bergmeyer H.U.
        • Scheibe P
        • Wahleveld A.W.
        Optimization of methods for aspartate aminotransferase and alanine aminotransferase..
        Clin. Chem. 1978; 24: 58-73
        • Szasz G.
        A kinetic photometric method for serum gamma-glutamyltranspeptidase.
        Clin. Chem. 1969; 15: 124-136
        • Szasz G.
        • Weimann G.
        • Stähler F.
        • Wahlefeld A.W.
        • Persijn J-P.
        New substrates for measuring gamma-glutamyltranspeptidase activity.
        Z. Klin. Chem. Klin. Biochem. 1974; 12: 228
        • Bowers Jr., G.N.
        • McComb R.B.
        A continuous spectrophotometric method for measuring the activity of serum alkaline phosphatase.
        Clin. Chem. 1966; 12: 70-89
        • Bergmeyer H.U.
        • Harder M.
        • Rej R.
        International Federation of Clinical Chemistry (IFCC).
        IFCC method for alanine amino-transferase. J. Clin. Chem. Clin. Biochem. 1986; 24: 481-495
        • Bergmeyer H.U.
        • Harder M.
        • Rej R.
        International Federation of Clinical Chemistry (IFCC).
        IFCC method for aspartate aminotransferase. J. Clin. Chem. Clin. Biochem. 1986; 24: 497-510
        • Persijn J-P.
        • van der Silk W.
        A new method for the determination of 7-glutamyltransferase in serum.
        J. Clin. Chem. Clin. Biochem. 1976; 14: 421-427
        • Mathieu M.
        • Bretaudiere J.P.
        • Galteau M.M.
        • Guidollet J.
        • Lalegerie P.
        • Bailly M.
        • Buret P.
        • Dorche C.
        • Louisot P.
        • Schiele F.
        ̏Enzymology̋ commission. Current enzymology in clinical chemistry and recommendations for the measurement of catalytic activities in the serum at 30 degrees C..
        Ann. Biol, Clin. 1977; 35: 271-273
      4. SAS Institute Inc. Cary NC: SAS Institute. SAS/STAT User̓s Guide. 1989. Version 6, fourth edition. Volume 2: 891-996.

        • Pettit B.C.
        Identification of the diterpene esters in Arabica and Canephora coffees.
        J. Agri. Food Chem. 1987; 35: 549-551
        • Speer K.
        • Montag A.
        16-O-Methylcafestbl - ein neues Diterpen im Kaffee Erste Ergebnisse: Gehalte in Roh- und Röstkaffees..
        Dtsch. Lebensm. Rundsch. 1989; 85: 381-384
        • Speer K.
        • lewis T.
        • Montag A.
        16-0-Methylcafestol -ein neues Diterpen im Kaffee Freies und gebundenes 16-O-Methylcafestol..
        Z. Lebensm. Unters. Forsch. 1991; 192: 451-454
        • Nackunstz B.
        • Maier H.G.
        Diterpenoide im Kaffee.
        III Cafestol und Kahweol. Z. Lebensm. Unters. Forsch. 1987; 184: 494-499
        • Arnesen E.
        • Huseby N-E.
        • Brenn T.
        • Try K.
        The Troms0 Heart Study: distribution of, and determinants for, gamma-glutamyltransferase in a free-living population.
        Scand. J. Clin. Lab. Invest. 1986; 46: 63-70
        • Nilssen O.
        • F0rde O.H.
        • Brenn T.
        The Troms0 study.
        Distribution and population determinants of gamma-glutamyltransferase. Am. J. Epidemiol. 1990; 132: 318-326
        • Rudert C.S.
        • Galambos J.T.
        Alcohol-related symptoms.
        Clin. Gastroenterol. 1985; 14: 575-589
        • Ratnayake W.M.N.
        • Hollywood R.
        • O-Grady E.
        • Stavric B.
        Lipid content and composition of coffee brews prepared by different methods.
        Food Chem. Toxicol. 1993; 31: 263-269
        • Aro A.
        The effect of coffee on serum lipids and its clinical considerations.
        Cardiovasc. Risk Factors. 1993; 3: 238-243
        • Kark J.D.
        • Friedlander Y.
        • Kaufmann N.A.
        • Stein Y.
        Coffee, tea, and plasma cholesterol: the Jerusalem Lipid Research Clinic prevalence study.
        Br. Med. J. 1985; 291: 699-704
        • Keys A.
        • Aravanis C.
        • Blackburn H.
        • Buzina R.
        • Dontas A.S.
        • Fidanza F.
        • Karvonen M.J.
        • Menotti A.
        Serum cholesterol and cancer mortality in the seven countries study.
        Am. J. Epidemiol. 1985; 121: 870-883
        • Aro A.
        • Kostiainen E.
        • Huttunen J.K.
        • Seppala E.
        • Vapaatalo H.
        Effects of coffee and tea on lipoproteins and prostanoids.
        Atherosclerosis. 1985; 57: 123-128
        • Burr M.L.
        • Gallagher J.E.J.
        • Butland B.K.
        • Bolton C.H.
        • Downs L.G.
        Coffee, blood pressure and plasma lipids: a randomized controlled trial.
        Eur. J. Clin. Nutr. 1989; 43: 477-483
      5. World Health Organization. 1987. Table: Age-standardized death rates for selected causes, by sex, latest available year. In World Health Statistics Annual, Geneve. 342-349.